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      Serum bicarbonate and cardiovascular events in hypertensive adults: results from the Systolic Blood Pressure Intervention Trial

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          Low serum bicarbonate level is associated with increased mortality, but its role as a predictor of cardiovascular disease (CVD) is unclear. This study evaluates the association between serum bicarbonate concentration and CVD and whether the effect of intensive blood pressure (BP) lowering on CVD outcomes is modified by serum bicarbonate level.


          The Systolic Blood Pressure Intervention Trial (SPRINT) randomized participants to a systolic BP target <120 mmHg (intensive treatment) or <140 mmHg (standard treatment). The primary CVD outcome was a composite of nonfatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure and CVD death. Cox proportional hazards models adjusted for demographic, clinical and laboratory characteristics were used to evaluate the association of interest in 9334 SPRINT participants ( NCT01206062).


          Over a median follow-up of 3.33 years (interquartile range 2.87–3.87 years), 618 (6.6%) participants experienced a primary CVD outcome. Participants with serum bicarbonate <22 mEq/L had a significantly higher risk of the primary CVD outcome (hazard ratio 1.54; 95% confidence interval 1.11–2.14, P = 0.01), compared with participants with bicarbonate 22–26 mEq/L. The magnitude of the CVD risk reduction with intensive BP lowering was similar across bicarbonate strata (P-value for interaction = 0.97).


          In hypertensive individuals, serum bicarbonate level <22 mEq/L was associated with an increased CVD risk. The effect of intensive BP lowering on CVD outcomes was not modified by the serum bicarbonate level.

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          Most cited references 25

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          The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT).

          High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes, including coronary heart disease, stroke, decompensated heart failure, chronic kidney disease, and decline in cognitive function. Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg. Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease. However, the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear, and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large, definitive clinical trial. To describe the design considerations of the Systolic Blood Pressure Intervention Trial (SPRINT) and the baseline characteristics of trial participants. The Systolic Blood Pressure Intervention Trial is a multicenter, randomized, controlled trial that compares two strategies for treating systolic blood pressure: one targets the standard target of <140 mm Hg, and the other targets a more intensive target of <120 mm Hg. Enrollment focused on volunteers of age ≥50 years (no upper limit) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease, chronic kidney disease, 10-year Framingham cardiovascular disease risk score ≥15%, or age ≥75 years. The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups: participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), participants with a history of cardiovascular disease, and participants 75 years of age or older. The primary outcome is first the occurrence of a myocardial infarction (MI), acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. Secondary outcomes include all-cause mortality, decline in kidney function or development of end-stage renal disease, incident dementia, decline in cognitive function, and small-vessel cerebral ischemic disease. Between 8 November 2010 and 15 March 2013, Systolic Blood Pressure Intervention Trial recruited and randomized 9361 people at 102 clinics, including 3331 women, 2648 with chronic kidney disease, 1877 with a history of cardiovascular disease, 3962 minorities, and 2636 ≥75 years of age. Although the overall recruitment target was met, the numbers recruited in the high-risk subgroups were lower than planned. The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants, including those with prior cardiovascular disease, chronic kidney disease, and those aged ≥75 years. © The Author(s) 2014.
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            Global Cardiovascular and Renal Outcomes of Reduced GFR

            The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
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              Effects of Intensive BP Control in CKD


                Author and article information

                Nephrology Dialysis Transplantation
                Oxford University Press (OUP)
                August 14 2019
                August 14 2019
                [1 ]Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA
                [2 ]Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA
                [3 ]Veterans Affairs Salt Lake City Healthcare System, University of Utah Health, Salt Lake City, UT, USA
                [4 ]Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
                [5 ]VA Medical Center, George Washington University, Washington, DC, USA
                [6 ]Division of Nephrology, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA
                [7 ]Nephrology, New Mexico VA Health Care System, Albuquerque, NM, USA
                [8 ]Medicine, Nephrology, Tufts Medical Center, Boston, MA, USA
                © 2019


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